YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex

Milos Kostic, Judith T. M. L. Paridaen, Katherine R. Long, Nereo Kalebic, Barbara Langen, Nannette Gruebling, Pauline Wimberger, Hiroshi Kawasaki, Takashi Namba, Wieland B. Huttner

OnderzoeksoutputAcademicpeer review

21 Citaten (Scopus)
159 Downloads (Pure)

Samenvatting

Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major down-stream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.

Originele taal-2English
Pagina's (van-tot)1103-1118.e6
Aantal pagina's22
TijdschriftCell reports
Volume27
Nummer van het tijdschrift4
DOI's
StatusPublished - 23-apr-2019

Citeer dit